It is well known that medical treatments which use extracorporeal blood circulation devices such as artificial kidneys and pump-oxygenators often cause hemolysis, i.e., the liberation of hemoglobin from red blood cells. Free hemoglobin in the blood resulting from hemolysis may cause various kinds of complications in the human body. Although free hemoglobin will normally bind with haptoglobins, a group of glyproteins in serum, to form complexes which will eventually be disposed of in the reticuloendothelial system, the extent of hemolysis is often greater than the capability of disposition thereof. When there is more free hemoglobin in the blood than can be disposed of, the free hemoglobin acts as a histotoxic substance which can ultimately cause a renal insufficiency.
Similarly, hemolytic anemia, which is a type of autoimmune disease, may also cause a large volume of free hemoglobin to be liberated into blood plasma and lead to various kinds of complications.
It is believed that medical complications associated with free hemoglobin can be prevented by removing free hemoblobin from the blood. In the past, semi-permeable membranes have been used to separate and remove free hemoglobin from other blood components. Efforts to remove free hemoglobin from blood have also been made using absorbent materials which will selectively absorb the free hemoglobin.
Activated charcoal is a material that has been practically used as an absorbent for hematocatharsis, however, the material has little or no affinity for hemoglobin and therefore has not been used for this purpose.
Absorbents for free hemoglobin which are presently known are based upon natural haptoglobin. Heretofore, haptolglobin has been bound to insoluble carriers in an effort to take advantage of haptoglobin's natural affinity for selectively binding free hemoglobin. This type of absorbent is disclosed for example, in Japanese Patent Publications, Nos. 55-4417 and 56-51780.
The haptoglobin-based absorbents have not proved to be satisfactory for a number of reasons. In order to obtain an effective absorbent, it is necessary that the haptoglobin retain its activity after it has been affixed to an insoluble carrier. However, it has proven to be extremely difficult to isolate the haptoglobin from separated, refined blood plasma and affix the naturally occurring glycoprotein to the surface of a carrier without rendering the substance inactive. In fact, no practical method has yet been found. Even in those instances where active haptoglobin has successfully been affixed to the carrier, the passage of time often leads to a decrease in activity of the absorbent. As result, the method of absorbing free hemoglobin with haptoglobin-based carriers has not met with a great deal of success.
Another disadvantage of the haptoglobin-based absorbents is that they are deactivated upon sterilization. Pre-sterilization, however, is particularly important for medical uses.
Accordingly, it is one primary objective of the present invention to provide absorbents which selectively absorb free hemoglobin and which are easily produced.
Another objective of this invention is to provide absorbents for free hemoglobin which remain effective upon sterilzation.
These and other objectives of the present invention will become apparent from the specification.